Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The apparent renal clearance of intravenously injected [14C]glycocholate and [3H]chenodeoxycholate-3-sulphate was estimated in 22 patients with cholestasis. The degree of protein binding of the isotopes in serum from these patients was determined. The effects of pharmacological agents, changes in urine flow rate and pH on renal clearance was studied. 2. The mean renal clearance of [14C]glycocholate was 1 . 7 +/- 0 . 4 ml/min (mean +/- SEM), and that of [3H]chenodeoxycholate-3-sulphate was 6 . 4 +/- 0 . 9 ml/min. [14C]Glycocholate was 80 . 1% protein bound and [3H]chenodeoxycholate-3-sulphate 96 . 5% protein bound. 3. Comparisons of the observed clearance rates with those calculated on the basis of glomerular filtration of the unbound fraction suggest that whereas [14C]glycocholate is predominantly reabsorbed by the renal tubules, [3H]chenodeoxycholate-3-sulphate appears in the urine mainly as the result of tubular secretion. 4. Probenecid, ethacrynic acid, frusemide and bendrofluazide decreased the clearance of both bile acids, implying competition for secretion via the proximal tubular organic acid secretory pathway between these compounds and bile acids. 5. Passive non-ionic diffusion does not seem to be an important mechanism in the renal excretion of bile acids as changes in urine flow rate and pH did not influence bile acid clearance. 6. A greater affinity of the proximal tubular organic acid secretory pathway for sulphated than for non-sulphated bile acids may explain the higher observed renal clearance rate of sulphated bile acids.
 ...
PMID:Urinary excretion of bile acids in cholestasis: evidence for renal tubular secretion in man. 729 39

Fasting serum levels of glycocholic acid were measured in 142 patients with benign diffuse liver diseases. A total of 63.4% of the whole group of patients, 86.6% of the cirrhotic patients and 31.7% of the noncirrhotic patients had increased serum levels of glycocholic acid. There were significant correlations with blood liver tests associated with liver disease severity such as prothrombin activity and albumin. There were highly significant differences in glycocholic acid levels according to the histological severity of the liver disease, especially when patients with cirrhosis or chronic active hepatitis were compared to the remaining patients and controls. However, discriminant analysis showed that prothrombin activity and albumin were better than glycocholic acid in predicting the histological severity of liver disease. Glycocholic acid serum levels were relatively independent of cholestasis and cytolysis and appeared to be more linked to liver dysfunction. In conclusion, fasting glycocholic acid measurement can be useful in the evaluation and follow-up of liver diseases as a marker of histological severity, and used in addition to other liver tests.
 ...
PMID:Clinical value of the determination of fasting glycocholic acid serum levels in patients with liver diseases. A comparison with standard liver tests. 850 Jul 13

We investigated the effects of ursodeoxycholic acid (UDCA; 60 microg/day/100 g b.wt.) on the impairment induced by maternal obstructive cholestasis during pregnancy (OCP) in the rat placenta-maternal liver tandem excretory pathway. A blunted catheter was implanted in the common bile duct on day 14 of pregnancy, and the tip was cut on day 21. [(14)C]Glycocholate (GC) was then administered through the umbilical artery of "in situ" perfused placenta (placental transfer test) or through the maternal jugular vein (biliary secretion test), and GC bile output was measured. OCP impaired both GC placental transfer and maternal biliary secretion. UDCA moderately improved the latter but had a more marked beneficial effect on GC placental transfer. Histological examination revealed trophoblast atrophy and structural alterations, e.g., loss of apical membrane microvilli in OCP placentas. Gene expression level was investigated by real-time quantitative reverse transcription-polymerase chain reaction and Western blot analysis. OCP reduced both placental lactogen II (a trophoblast-specific gene) mRNA and the functional amount of epithelial tissue, determined by transplacental diffusion of antipyrin. Using a rapid filtration technique, impairment in the ATP-dependent GC transport across trophoblast apical plasma membranes obtained from OCP placentas was found. UDCA partially prevented all these changes. The expression level of organic anion transporters Oatp1, Oatp2, and Oatp4, and multidrug resistance-associated proteins Mrp1, Mrp2, and Mrp3 in whole placenta were not affected or were moderately affected by OCP but greatly enhanced by UDCA. In summary, UDCA partially prevents deleterious effects of OCP on the rat placenta-maternal liver tandem excretory pathway, mainly by preserving trophoblast structure and function.
 ...
PMID:Effect of ursodeoxycholic acid on the impairment induced by maternal cholestasis in the rat placenta-maternal liver tandem excretory pathway. 1260 35